Identification and quantitation of numerous biological molecules to generate a complex molecular profile is required for diagnosis, monitoring, and prognostic evaluation of complex diseases such as cancer. Despite outstanding progress in the area of cancer biology, significant challenges remain in translating biological knowledge of cancer surface markers into clinically relevant devices that could be used as diagnostic or monitoring tools for cancer management. Developing high-throughput and low cost diagnostic cell and tissue analysis for disease detection has remained a challenge.
For example, breast cancer is the most diagnosed cancer in women, and it has been found that developing breast cancers shed transformed cells into the blood, with more malignant breast cancer cells appearing in the blood in later stages. It is believed by many that early detection of circulating breast cancer cells might improve diagnosis of early breast cancer and ultimately reduce breast cancer-related deaths. Therefore, significant efforts have been made toward the development of methods and devices for detecting circulating breast cancer cells in blood.
Circulating tumor cells (CTC's) have long been analyzed ex vivo by flow cytometry and fluorescence microscopy to measure characteristic cell surface markers, such as epithelial cell adhesion marker (EpCAM), a general purpose epithelial cell marker that is common to circulating tumor cells. Many of these techniques, however, are expensive and time consuming, often requiring several days to generate results.
More recently, it has been found that small bundles of single wall carbon nanotubes (SWCNT), ˜10 nm diameter, lithographically patterned between two electrodes, with adsorbed monoclonal antibodies, will display a sensitivity to a single cancer cell in 1 μL of blood. Moreover, such devices have the potential to detect the presence of cancer cells in blood in a matter of minutes, rather than days as is often the case with other methodologies. However, the use of single or small bundles of SWCNT's presents challenges in a clinical setting due to the difficultly in fabricating such single or small bundle SWCNT samples, and ensuring that the cancer cells are bridging the electrodes to achieve reliable detection. Furthermore, the use of nanoscale devices precludes the use of large blood volumes that are typically analyzed in a clinical setting.
Therefore, a need continues to exist in the art for an improved methodology and device for detecting cancer cells and other cellular targets in blood and other bodily sources.